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Diss Factsheets

Toxicological information

Developmental toxicity / teratogenicity

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Administrative data

Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods with acceptable restrictions

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1998
Report date:
1998

Materials and methods

Test material

Constituent 1
Chemical structure
Reference substance name:
Prasterone
EC Number:
200-175-5
EC Name:
Prasterone
Cas Number:
53-43-0
Molecular formula:
C19H28O2
IUPAC Name:
(3S,8R,9S,10R,13S,14S)-3-hydroxy-10,13-dimethyl-1,2,3,4,7,8,9,11,12,14,15,16-dodecahydrocyclopenta[a]phenanthren-17-one
Test material form:
solid
Details on test material:
white solid

Test animals

Species:
other: rat & rabbit
Strain:
other: CD rat & New Zealand White rabbit

Administration / exposure

Route of administration:
other: oral (no further specifications)
Vehicle:
not specified
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
Rabbits received DHEA during GD7-20 (GD0 - day of observed mating).
Rats received DHEA during GD6-17 (GD0 = day of vaginal plug)
Frequency of treatment:
Daily
Duration of test:
10 days
Doses / concentrationsopen allclose all
Dose / conc.:
0 mg/kg bw/day
Remarks:
rat, Control, group 1
Dose / conc.:
5 mg/kg bw/day
Remarks:
rat, group 2
Dose / conc.:
15 mg/kg bw/day
Remarks:
rat, group 3
Dose / conc.:
50 mg/kg bw/day
Remarks:
rat, group 4
Dose / conc.:
0 mg/kg bw/day
Remarks:
rabbit, group 1
Dose / conc.:
20 mg/kg bw/day
Remarks:
rabbit, group 2
Dose / conc.:
50 mg/kg bw/day
Remarks:
rabbit, group 3
Dose / conc.:
125 mg/kg bw/day
Remarks:
rabbit, group 4
No. of animals per sex per dose:
Not specified
Control animals:
yes, concurrent no treatment

Examinations

Maternal examinations:
CAGE SIDE OBSERVATIONS: No data

DETAILED CLINICAL OBSERVATIONS: No data

BODY WEIGHT: No data


FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): No data

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data


POST-MORTEM EXAMINATIONS: Yes
- Rabbits: fetuses were obtained by cesariian section on gestation day 29
- Rats: fetuses were obtained by cesarean section on GD20

Results and discussion

Results: maternal animals

General toxicity (maternal animals)

Mortality:
no mortality observed

Maternal developmental toxicity

Number of abortions:
not specified
Pre- and post-implantation loss:
effects observed, treatment-related
Description (incidence and severity):
in rats, embryolethality and increased early resorptions occurred at all dose levels including complete litter loss in 2 litters at 5 mg/kg/day and 3 litters each at 15 and 50 mg/kg/day.
Total litter losses by resorption:
effects observed, treatment-related
Description (incidence and severity):
in rats, embryolethality and increased early resorptions occurred at all dose levels including complete litter loss in 2 litters at 5 mg/kg/day and 3 litters each at 15 and 50 mg/kg/day. Litter loss was confirmed after immersion of uteri in ammonium sulfide solution.
Early or late resorptions:
effects observed, treatment-related
Description (incidence and severity):
in rats, embryolethality and increased early resorptions occurred at all dose levels including complete litter loss in 2 litters at 5 mg/kg/day and 3 litters each at 15 and 50 mg/kg/day.
Details on maternal toxic effects:
rabbits: There were no effects on embryonic and fetal development

Effect levels (maternal animals)

open allclose all
Dose descriptor:
NOAEL
Remarks:
rabbit
Effect level:
125 mg/kg bw/day
Based on:
test mat.
Basis for effect level:
other: no effects on embryonic and fetal development
Dose descriptor:
LOAEL
Remarks:
rat
Effect level:
5 mg/kg bw/day
Based on:
test mat.
Basis for effect level:
early or late resorptions
total litter losses by resorption

Maternal abnormalities

Abnormalities:
not specified

Results (fetuses)

Skeletal malformations:
effects observed, treatment-related
Description (incidence and severity):
in rats: Increased numbers of litters with bent ribs occurred at all concentrations. Increased numbers of litters with reduced ossification of cervical arches was seen at 50 mg/kg/day
Description (incidence and severity):
in rabbits, there were no effects on embryonic or fetal development

Effect levels (fetuses)

open allclose all
Dose descriptor:
NOAEL
Remarks:
rabbit
Effect level:
125 mg/kg bw/day
Based on:
test mat.
Basis for effect level:
other: no effects on embryonic and fetal development
Dose descriptor:
LOAEL
Remarks:
rat
Effect level:
5 mg/kg bw/day
Based on:
test mat.
Sex:
not specified
Basis for effect level:
reduction in number of live offspring
changes in postnatal survival
skeletal malformations

Fetal abnormalities

Abnormalities:
effects observed, treatment-related
Localisation:
skeletal: rib
skeletal: vertebra

Overall developmental toxicity

Developmental effects observed:
yes
Lowest effective dose / conc.:
5 mg/kg bw/day
Treatment related:
yes
Relation to maternal toxicity:
not specified
Dose response relationship:
yes
Relevant for humans:
not specified

Applicant's summary and conclusion

Conclusions:
No effects on embryonic or fetal development were observed in New Zealand White rabbits , dosed orally during GD7-20 with DHEA at dose levels of 0, 20, 50 or 125 mg/kg/day.
In the same study, CD rats were dosed orally with DHEA during GD6-17 at dose levels 0, 5, 15 or 50 mg/kg/day. Embryolethality and increased early resorptions occurred at all dose levels in rats, including complete litter loss. Skeletal malformations were also observed. DHEA may may interfere with the energy requirements of the developing embryo or perturb to hormonal balance necessary to maintain implantation.